Tests venetoclax with ibrutinib and rituximab in mantle cell lymphoma

Who can take part

• Histologically confirmed diagnosis of MCL according to WHO classification
• Creatinine ≤ 2 mg/dL or eGFR ≥ 50 mL/min
• Written informed consent form according to ICH/EU GCP and national regulations
• Sexually active men with female partners of child-bearing potential potential must agree to use highly effective contraceptives
• previously untreated stage II-IV (Ann Arbor), previous local therapyi e.g. radiation therapy to single lesion is eligible, a limited pre-phase treatment with steroids for patients at need is allowed (s. treatment)
• ≥ 60 years and not suitable for autologous SCT
• At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations
• ECOG performance status ≤ 2
• Absolute neutrophil count (ANC) ≥ 1000 cells/μL
• Platelets ≥75.000 cells/μL
• Transaminases (AST and ALT) ≤3 x ULN
• Total bilirubin ≤ 2 x ULN unless other reason known (Gilbert- Meulengracht-Syndrome)

Who cannot take part

• Major surgery within 4 weeks prior to first dose
• History of stroke or intracranial hemorrhage within 6 months prior to first dose
• Treatment with strong or moderate CYP3A4/5 inhibitors/inducers within 7 days before first dose and during Venetoclax and Ibrutinib intake
• Vaccinated with live, attenuated vaccines within 4 weeks prior to first dose
• Known bleeding disorder (e.g. von Willebrand disease; hemophilia) Serious concomitant disease interfering with a regular therapy according to the study protocol
• any other significant medical condition interfering with the conduct of the trial treatment
• Patients with unresolved hepatitis B or C infection or known HIV positive infection (mandatory test) Concomitant or previous malignancies within the last 3 years other than basal cell skin cancer, Prostate cancer in remission with PSA within normal range or in situ uterine cervix cancer
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk
• Cardiac (Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below LLN)
• Patients requiring double platelet inhibition, e.g due to cardiovascular intervention
• clinically significant pulmonary dysfunction interfering with the conduct of the trial treatment
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon)
• Known CNS involvement of MCL